As a type of sensors, a biosensor has been known. The biosensor is a measuring device utilizing an excellent biomolecular recognition ability of a living body (organism) or biomolecule and recently expected to be widely applied to various fields including not only a medical field but also an environmental field, a foodstuff field, etc.
Generally, the biosensor is constituted by a trapping substance for recognizing and trapping a substance to be subjected to measurement (hereinafter referred to as a “target substance”) and a detecting device for detecting a physical/chemical change caused during the recognition and trapping of the target substance and converting the change into a detectable signal such as an electric signal or an optical signal. In the living body, as a combination of substances having a mutual affinity, there are combinations of, e.g., enzyme-substrate, antigen-antibody, and DNA-DNA. The biosensor utilizes such a principle that one of the substances of the combination is fixed or carried on a supporting member to be used as a component of the trapping substance and thus the other substance is selectively measurable. Further, as the detecting device, there have been proposed detecting devices of various types including an oxygen electrode, a hydrogen peroxide electrode, an ion electrode, an ion-sensitive field-effect transistor (ISFET), a thermistor, etc. In recent years, a quartz resonator, a surface-acoustic-wave (SAW) device, a plasmon resonator, and the like are used in some cases.
Of the various sensors, a sensor including a detection system utilizing plasmon resonance has the following advantages (1) and (2):
(1) it is possible to simply constitute an assay since there is no need to use a labeled molecule such as a fluorescent dye, and
(2) it is possible to directly effect real-time monitoring of a process of adsorption reaction onto surfaces of metal fine particles.
Therefore, such a measuring method is expected to be applied to various assays.
In the measuring method, detection of a substance present in the neighborhood of metal fine particles is effected utilizing such a phenomenon that a characteristic resonance spectrum appears by localized plasmon resonance induced when metal fine particles of gold, silver, or the like are fixed on a surface of a substrate and light is incident on the metal fine particles. It has been known that a waveform of the resonance varies depending on a dielectronic constant of a medium present in the neighborhood of the metal fine particles.
An absorbance at a resonance peak becomes larger as the dielectric constant of the medium becomes larger, and shifts toward a long wavelength.
For example, Japanese Patent No. 3452837 has proposed a system using a gold colloid with about 20 nm of diameter is proposed. In the system, a refractive index of a medium located with a distance corresponding to an approximately diameter of metal fine particles fixed on a substrate is detected, so that it is possible to detect adsorption or deposition of a substance on the surfaces of the metal fine particles.
On the other hand, as proposed by Felicia Tam et al. (J. Phys. Chem. B., 2004, Vol. 108, No. 45, pp. 17290-17294), there is an example of device structure which aims at enhancement of detection capability by producing core shell type fine particles that are made by coating gold thin films on dielectric cores.
Further, Japanese Laid-Open Patent Application No. 2003-270132 has disclosed a sensor apparatus which includes a metal film provided with a plurality of openings to which a sensor material is fixed, a light source, and a light detector for detecting transmitted light or reflected light from the openings. In the sensor apparatus, the openings are periodically arranged in a first in-plane direction of the metal film.
However, when an affinity assay such as an immunoassay utilizing specify of an antigen-antibody reaction is effected by using a conventional device for detecting a target substance through utilization of the plasmon resonance, a sufficient detection sensitivity cannot be obtained in some cases. This problem regarding the detection sensitivity is one of problems to be solved in the case of applying a detecting method utilizing the plasmon resonance to the affinity assay in place of existing fluorescent immunoassay or chemiluminescent immunoassay. Accordingly, the problem regarding the detection sensitivity is a major problem for increasing use of a measuring method utilizing the localized plasmon resonance.